Three-dimensional homology model of GlcNAc-TV
glycosyltransferase

J 2016

Three-dimensional homology model of GlcNAc-TV glycosyltransferase

JANOŠ, Pavel, Stanislav KOZMON, Igor TVAROŠKA a Jaroslav KOČA

Základní údaje

Originální název

Three-dimensional homology model of GlcNAc-TV glycosyltransferase

Autoři

JANOŠ, Pavel (203 Česká republika, domácí), Stanislav KOZMON (703 Slovensko, domácí), Igor TVAROŠKA (703 Slovensko, domácí) a Jaroslav KOČA (203 Česká republika, garant, domácí)

Vydání

Glycobiology, Oxford University Press, 2016, 0959-6658

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.112

Kód RIV

RIV/00216224:14310/16:00089828

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1093/glycob/cww010

UT WoS

000384766000009

Klíčová slova anglicky

GlcNAc-TV; glycosyltransferase; homology model; N-glycosylation

Štítky

AKR, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 14. 4. 2017 16:00, Ing. Andrea Mikešková

Anotace

V originále

The enzyme UDP-N-acetylglucosamine: a-d-mannoside b-1-6 N-acetylglucosaminyltransferase V (GnT-V) catalyzes the transfer of GlcNAc from the UDP-GlcNAc donor to the a-1-6-linked mannose of the trimannosyl core structure of glycoproteins to produce the b-1-6-linked branching of N-linked oligosaccharides. b-1-6-GlcNAc-branched N-glycans are associated with cancer growth and metastasis. Therefore, the inhibition of GnT-V represents a key target for anti-cancer drug development. However, the development of potent and specific inhibitors of GnT-V is hampered by the lack of information on the three-dimensional structure of the enzyme and on the binding characteristics of its substrates. Here we present the first 3D structure of GnT-V as a result of homology modeling. Various alignment methods, docking the donor and acceptor substrates, and molecular dynamics simulation were used to construct seven homology models of GnT-V and characterize the binding of its substrates. The best homology model is consistent with available experimental data. The three-dimensional model, the structure of the enzyme catalytic site and binding information obtained for the donor and acceptor can be useful in studies of the catalytic mechanism and design of inhibitors of GnT-V.

Návaznosti

ED1.1.00/02.0068, projekt VaV

Název: CEITEC - central european institute of technology

LH13055, projekt VaV

Název: Multidisciplinární přístup k návrhu léčiv - Inhibice proteinů s návazností na cukry (Akronym: MADICA)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Multidisciplinární přístup k návrhu léčiv - Inhibice proteinů s návazností na sacharidy

Citovat

JANOŠ, Pavel, Stanislav KOZMON, Igor TVAROŠKA a Jaroslav KOČA. Three-dimensional homology model of GlcNAc-TV glycosyltransferase. Glycobiology. Oxford University Press, 2016, roč. 26, č. 7, s. 757-771. ISSN 0959-6658. Dostupné z: https://dx.doi.org/10.1093/glycob/cww010.

@article{1344264,
   author = {Janoš, Pavel and Kozmon, Stanislav and Tvaroška, Igor and Koča, Jaroslav},
   article_number = {7},
   doi = {http://dx.doi.org/10.1093/glycob/cww010},
   keywords = {GlcNAc-TV; glycosyltransferase; homology model; N-glycosylation},
   language = {eng},
   issn = {0959-6658},
   journal = {Glycobiology},
   title = {Three-dimensional homology model of GlcNAc-TV glycosyltransferase},
   url = {http://dx.doi.org/10.1093/glycob/cww010},
   volume = {26},
   year = {2016}
}

TY  - JOUR
ID  - 1344264
AU  - Janoš, Pavel - Kozmon, Stanislav - Tvaroška, Igor - Koča, Jaroslav
PY  - 2016
TI  - Three-dimensional homology model of GlcNAc-TV glycosyltransferase
JF  - Glycobiology
VL  - 26
IS  - 7
SP  - 757-771
EP  - 757-771
PB  - Oxford University Press
SN  - 09596658
KW  - GlcNAc-TV
KW  - glycosyltransferase
KW  - homology model
KW  - N-glycosylation
UR  - http://dx.doi.org/10.1093/glycob/cww010
L2  - http://dx.doi.org/10.1093/glycob/cww010
N2  - The enzyme UDP-N-acetylglucosamine: a-d-mannoside b-1-6 N-acetylglucosaminyltransferase V (GnT-V) catalyzes the transfer of GlcNAc from the UDP-GlcNAc donor to the a-1-6-linked mannose of the trimannosyl core structure of glycoproteins to produce the b-1-6-linked branching of N-linked oligosaccharides. b-1-6-GlcNAc-branched N-glycans are associated with cancer growth and metastasis. Therefore, the inhibition of GnT-V represents a key target for anti-cancer drug development. However, the development of potent and specific inhibitors of GnT-V is hampered by the lack of information on the three-dimensional structure of the enzyme and on the binding characteristics of its substrates. Here we present the first 3D structure of GnT-V as a result of homology modeling. Various alignment methods, docking the donor and acceptor substrates, and molecular dynamics simulation were used to construct seven homology models of GnT-V and characterize the binding of its substrates. The best homology model is consistent with available experimental data. The three-dimensional model, the structure of the enzyme catalytic site and binding information obtained for the donor and acceptor can be useful in studies of the catalytic mechanism and design of inhibitors of GnT-V.
ER  -

JANOŠ, Pavel, Stanislav KOZMON, Igor TVAROŠKA a Jaroslav KOČA. Three-dimensional homology model of GlcNAc-TV glycosyltransferase. \textit{Glycobiology}. Oxford University Press, 2016, roč.~26, č.~7, s.~757-771. ISSN~0959-6658. Dostupné z: https://dx.doi.org/10.1093/glycob/cww010.

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